title: Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells.
abstract: Early studies have shown that spindle oscillations are generated in the thalamus and are synchronized over wide cortical territories. More recent experiments have shown that this large-scale synchrony depends on the integrity of corticothalamic feedback. Previously proposed mechanisms emphasized exclusively intrathalamic mechanisms to generate the synchrony of these oscillations. In the present paper, we propose a cellular mechanism in which the synchrony is dependent of a mutual interaction between cortex and thalamus. This cellular mechanism is tested by computational models consisting of pyramidal cells, interneurons, thalamic reticular (RE) and thalamocortical (TC) relay cells, on the basis of voltage-clamp data on intrinsic currents and synaptic receptors present in the circuitry. The model suggests that corticothalamic feedback must operate on the thalamus mainly through excitation of GABAergic RE neurons, therefore recruiting relay cells essentially through inhibition and rebound. We provide experimental evidence for such dominant inhibition in the lateral posterior nucleus. In these conditions, the model shows that cortical discharges optimally evoked thalamic oscillations. This feature is essential to the present cellular mechanism and is also consistently observed experimentally. The model further shows that, with this type of corticothalamic feedback, cortical discharges recruited large areas of the thalamus because of the divergent cortex-to-RE and RE-to-TC axonal projections. Consequently, the thalamocortical network generated patterns of oscillations and synchrony similar to in vivo recordings. The model also emphasizes the important role of the modulation of the Ih current by calcium in TC cells. This property conferred a relative refractoriness to the entire network, a feature also observed experimentally, as we show here. Further, the same property accounted for various spatiotemporal features of oscillations, such as systematic propagation after low-intensity cortical stimulation, local oscillations, and more generally, a high variability in the patterns of spontaneous oscillations, similar to in vivo recordings. We propose that the large-scale synchrony of spindle oscillations in vivo is the result of thalamocortical interactions in which the corticothalamic feedback acts predominantly through the RE nucleus. Several predictions are suggested to test the validity of this model.
authors.affiliation: Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Québec G1K 7P4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Destexhe
authors.forename: D
authors.initials: D
authors.lastname: Contreras
authors.forename: M
authors.initials: M
authors.lastname: Steriade
mesh_terms: D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000502:physiology*; D005071:Evoked Potentials / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005246:Feedback; D007395:Interneurons / Q000502:physiology; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008959:Models, Neurological; D017966:Pyramidal Cells / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D009435:Synaptic Transmission; D013787:Thalamic Nuclei / Q000166:cytology / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D018079:Receptors, GABA; D017981:Receptors, Neurotransmitter